some drug side effects

2. Asterixis
Asterixis Other names Flapping tremor, liver flapSpecialtyNeurology
Asterixis is a tremor of the hand when the wrist is extended, sometimes said to resemble a bird
flapping its wings.
This motor disorder is characterized by an inability to maintain a position, which is demonstrated
by jerking movements of the outstretched hands when bent upward at the wrist.
The tremor is caused by abnormal function of the diencephalic motor centers in the brain, which
regulate the muscles involved in maintaining position.
Asterixis is associated with various encephalopathies due especially to faulty metabolism.[1] The
term derives from the Greek a, "not" and stērixis, "fixed position".
Asterixis is the inability to maintain posture due to a metabolic encephalopathy.[2]
This can be elicited on physical exam by having the patient extend their arms and bend their
hands back. With a metabolic encephalopathy, the patient is unable to hold their hands back
resulting in a “flapping” motion consistent with asterixis.
It can be seen in any metabolic encephalopathy e.g. chronic kidney failure, severe congestive
heart failure, acute respiratory failure and commonly in decompensated liver failure.

3. • TCAs can also cause sedation that results from blockade of
H1 histamine receptors, and
• orthostatic hypotension, due to blockade of α1 receptors on blood
vessels.
• Pharmacokinetics
• Tricyclics are rapidly absorbed from the gastrointestinal tract and
undergo first pass metabolism.
• They are highly protein bound and have a large volume of
distribution, resulting in a long half life of elimination
• that generally exceeds 24 hours and in the case of amitriptyline is
31 to 46 hours.7
• After metabolism by hepatic enzymes the metabolites, some of
which have pharmacological activity themselves, are conjugated
and excreted by the kidneys.

4. • The ingestion of large quantities of tricyclics in
self poisoning causes altered pharmacokinetics.
• Gastrointestinal absorption may be delayed
because of inhibition of gastric emptying and
significant enterohepatic recirculation prolongs
the final elimination.
• The amount of unbound tricyclic may also
increase if the overdose causes respiratory
depression resulting in an acidosis, which reduces
protein binding.

5. • The toxic effects of tricyclics are caused by
four main pharmacological properties:
1. Inhibition of norepinephrine reuptake at nerve terminals.
2. Direct α adrenergic block.
3. A membrane stabilising or quinidine-like effect on the
myocardium.
4. Anticholinergic action.

6. What is gray baby syndrome?
The syndrome is a result of chloramphenicol
impairing myocardial contractility by directly interfering with
myocardial tissue respiration and oxidative phosphorylation.
Plasma binding protein levels are lower in the newborn than in
the adult and gradually increase with age.
 At birth, human serum albumin (HSA) concentrations are
close to adult levels (75%-80%), while alpha 1-acid glycoprotein
(AAG) is initially half the adult concentration.

8.  Chloramphenicol antibiotic is dangerous for babies because of its high
toxicity level.
 Unfortunately, infants and babies don’t have the liver enzymes needed to
metabolize large doses of this medication.
 Since their little bodies can’t break down the drug, toxic levels of the
antibiotic can build up in their bloodstreams.
 Gray baby syndrome can develop if the antibiotic is given directly to
babies.
 They may also be at risk for this condition if the antibiotic is given to their
mother during labor or at some point during the pregnancy.

9. • Chloramphenicol has been used for
 The treatment of meningitis in penicillin-allergic patients,
 The for meningitis caused by penicillin-resistant pneumococci, and as an oral alternative
when the use of parenteral therapy is impossible.
 It also has been used to treat infections caused by vancomycin-resistant enterococci that
are resistant to other antibiotic regimens

10. • chloramphenicol has been used in antipseudomonal combinations, notably
with streptomycin against Pseudomonas mallei and with doxycycline
against P pseudomallei
Why antacid should not be used for longer time?
• Antacids (for example, calcium carbonate) when consumed in high doses
and for long periods of time may cause acid rebound.
• Acid rebound is a condition in which the stomach produces even more
acid after the consumption of foods and drinks.
• Fortunately, the effects of acid rebound are not clinically important.
• What happens if you take antacids for too long?
• Many antacids — including Maalox, Mylanta, Rolaids and Tums — contain
calcium.
• If you take too much or take them for longer than directed, you could get
an overdose of calcium. Too much calcium can cause: nausea.

11. • Why do PPIs need to be taken on an empty stomach?
• Are most effective when taken on an empty stomach.
• PPIs circulate in the blood to block the stomach's acid
pumps, which are activated when you eat.
• Which proton pump inhibitor is safest?
• “In a large placebo-controlled randomized trial, we
found that pantoprazole is not associated with any
adverse event when used for 3 years, with the possible
exception of an increased risk of enteric infections
•

12. • What happens if you take proton pump inhibitors
long term?
• Although PPIs have had an encouraging safety
profile, recent studies regarding the long-term
use of PPI medications have noted potential
adverse effects,
• including risk of fractures, pneumonia,
Clostridium difficile diarrhea, hypomagnesemia,
vitamin B12 deficiency, chronic kidney disease,
and dementia.

13. • Age >50 yrs
 Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus
vancomycin*
• Impaired cellular immunity
• Vancomycin plus ampicillin plus either cefepime or meropenem
• Recurrent meningitis
• Vancomycin plus cefotaxime or ceftriaxone

14. • Chloramphenicol is active against a variety of
organisms,
including bacteria,
spirochetes,
rickettsiae,
chlamydiae, and
mycoplasmas.
• Most gram-positive and gram-negative aerobic
bacteria are inhibited by chloramphenicol, although
other therapeutic agents are available for use against
most of these pathogens.

15. • Chloramphenicol is one of the most active antibiotics against anaerobic
bacteria, including Bacteroides fragilis, but clindamycin, metronidazole,
and imipenem are used more frequently to treat infections caused by these
bacteria.

16. Mechanism of CAF
• Chloramphenicol inhibits protein synthesis by binding to the 50S subunit of
the 70S ribosome, producing a static effect against most sensitive
microorganisms.

17. • Why do diabetics have fat babies?
• This causes the baby's pancreas to make extra insulin to get rid of the blood
glucose. Since the baby is getting more energy than it needs to grow and
develop, the extra energy is stored as fat. This can lead to macrosomia, or a
"fat" baby.
• Why infants of diabetic mothers develop macrosomia? Large birthweight is
called macrosomia. Babies weighing more than 4kg (8lb 8oz) at birth are
considered macrosomic.
• What birth defects are caused by diabetes?
• Among the defects in children born to women with diabetes are
 heart problems,
 brain and
 spinal defects,
 oral clefts,
 kidney and
 gastrointestinal tract defects, and
 limb deficiencies.

18. • Why do Type 1 diabetics have big babies?
• Women with type 1 diabetes are at higher risk
of complications in pregnancy mainly because
glucose levels are harder to control.
• Their babies are more likely to be larger than
average, which can mean a difficult delivery,
and need special care when born.

19. • It is bactericidal against some meningeal pathogens such as
– Haemophilus influenzae,
– Streptococcus pneumoniae, and
– Neisseria meningitidis,
• Chloramphenicol is metabolized primarily by the liver, where
it is conjugated with glucuronic acid and is excreted in this
inactive form by the kidney
• Main point
 Children's lack of glucuronic enzyme for the metabolism of
CAP & resulted in excess drug in the blood circulation and
cause baby skin to gray in colour which is gray baby
syndrome.

20. • The most important toxic effects of chloramphenicol occur in the bone
marrow.
• Bone marrow suppression.
• The other major toxic effect of chloramphenicol is the gray baby syndrome
in neonates, which is characterized by abdominal distension, vomiting,
flaccidity, cyanosis, circulatory collapse, and death.
• This syndrome also has been recognized in toddlers and after overdoses in
adults.
• It generally is associated with serum concentrations of chloramphenicol
greater than 50 mcg/dL and may present with unexplained metabolic
acidosis, irregular respiration, and circulatory collapse, usually within 3 to
5 days of the initiation of therapy

21. • Common side effects of chloramphenicol include:
 not enough red blood cells produced (aplastic anemia)
 bone marrow suppression.
 diarrhea.
 inflammation of the small intestine and the colon (enterocolitis)
 accumulation of chloramphenicol especially in newborns (gray syndrome)
 headache.
 nausea.
 nightmares.
How can chloramphenicol cause enterocolitis?

22. • long-term use of PPI medications have noted potential adverse effects,
• including
• risk of fractures,
• pneumonia,
• Clostridium difficile diarrhea,
• hypomagnesemia,
• vitamin B12 deficiency,
• chronic kidney disease, and
• dementia

23. • Valium (diazepam) is a benzodiazepine derivative. The chemical name of
diazepam is 7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-
benzodiazepin2-one. It is a colorless to light yellow crystalline compound,
insoluble in water. The empirical formula is C16H13ClN2O and the
molecular weight is 284.75. The structural formula is as follows:
• Valium is available for oral administration as tablets containing 2 mg, 5 mg
or 10 mg diazepam.
• Why diazepam is not recommended in patients with epilepsy who under
6th months?is the drug safe to use in nursing mother?(10 birr card is waiting
for you for 3 minutes)

24. CLINICAL PHARMACOLOGY
• Diazepam is a benzodiazepine that exerts anxiolytic, sedative, muscle-relaxant,
anticonvulsant and amnestic effects.
• Most of these effects are thought to result from a facilitation of the action of gamma
aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous
system.
• Pharmacokinetics
• Absorption :After oral administration >90% of diazepam is absorbed and the
average time to achieve peak plasma concentrations is 1 – 1.5 hours with a range of
0.25 to 2.5 hours.
• Absorption is delayed and decreased when administered with a moderate fat meal.
• In the presence of food mean lag times are approximately 45 minutes as compared
with 15 minutes when fasting.
• There is also an increase in the average time to achieve peak concentrations to
about 2.5 hours in the presence of food as compared with 1.25 hours when fasting.
• This results in an average decrease in Cmax of 20% in addition to a 27% decrease
in AUC (range 15% to 50%) when administered with food

25. • Wheezy infants do not respond to bronchodilators
despite evidence of functioning β-adrenoceptors.
• This is because the predominant a etiology, bronchiolitis, is
characterised by small airway oedema and
• increased mucus, for which β2-agonists are ineffective.
• Infants with bronchiolitis do not respond to salbutamol
 because they do not have β2-adrenoceptors
• β2-adrenoceptors mediate their action through G protein-
coupled adenylate cyclase activation, increased cAMP and the
inhibition of calcium release from intracellular stores,
ultimately leading to smooth muscle relaxation and
bronchodilation.

27. Dobutamine is a β-adrenergic agonist that
stimulates
» β1-adrenergic,
» β2-adrenergic, and
» α1-adrenergic receptors.
• Cardiac contractility is increased by virtue of its β1 and
α1 effects, but because the α1-adrenergic effects are generally
counterbalanced by the β2 actions,
• Generally little change in blood pressure.

28. • DRUG INTERACTIONS
• Because dopamine is metabolized by monoamine oxidase (MAO), inhibition of this enzyme prolongs and potentiates the
effect of dopamine. Patients who have been treated with MAO inhibitors within two to three weeks prior to the
administration of dopamine HCl should receive initial doses of dopamine HCl no greater than one-tenth (1/10) of the usual
dose.
• Concurrent administration of dopamine HCl and diuretic agents may produce an additive or potentiating effect on urine flow.
• Tricyclic antidepressants may potentiate the pressor response to adrenergic agents.
• Cardiac effects of dopamine are antagonized by beta-adrenergic blocking agents, such as propranolol and metroprolol. The
peripheral vasoconstriction caused by high doses of dopamine HCl is antagonized by alpha-adrenergic blocking agents.
Dopamine-induced renal and mesenteric vasodilation is not antagonized by either alpha- or beta-adrenergic blocking agents.
• Haloperidol appears to have strong central antidopaminergic properties. Haloperidol and haloperidol-like drugs suppress the
dopaminergic renal and mesenteric vasodilation induced at low rates of dopamine infusion.
• Cyclopropane or halogenated hydrocarbon anesthetics increase cardiac autonomic irritability and may sensitize
the myocardium to the action of certain intravenously administered catecholamines, such as dopamine. The interaction
appears to be related both to pressor activity and to the beta-adrenergic stimulating properties of these catecholamines, and
may produce ventricular arrhythmias. Therefore, EXTREME CAUTION should be exercised when administering dopamine
HCl to patients receiving cyclopropane or halogenated hydrocarbon anesthetics. It has been reported that results of studies in
animals indicated that dopamine-induced ventricular arrhythmias during anesthesia can be reversed by propranolol.
• The concomitant use of vasopressors, vasoconstricting agents and some oxytocic drugs may result in severe persistent
hypertension. See Labor and Delivery below.
• Administration of phenytoin to patients receiving dopamine HCl has been reported to lead to hypotension and bradycardia. It
is suggested that in patients receiving dopamine HCl, alternatives to phenytoin should be used if anticonvulsant therapy is
needed.
•